Endomicroscopy and Endocytoscopy in IBD




Two types of endomicroscopy systems exist. One is integrated into a standard, high-resolution endoscope and one is probe-based, capable of passage through the working channel of a standard endoscope. Endocytoscopy allows visualization of the superficial mucosal layer. Endoscope-integrated and probe-based devices allow magnification of the mucosa up to 1400-fold. Endomicroscopy can differentiate histologic changes of Crohn disease and ulcerative colitis in vivo in real time. Endocytoscopy can discriminate mucosal inflammatory cells, allowing determination of histopathologic activity of ulcerative colitis. Molecular imaging with fluorescence-labeled probes against disease-specific receptors will enable individualized management of inflammatory bowel diseases.


Key points







  • •

    Two types of endomicroscopy systems exist. One is integrated into a standard, high-resolution endoscope (integrated confocal laser endomicroscopy [iCLE]) and one is probe-based, capable of passage through the working channel of a standard endoscope (probe-based CLE [pCLE]).


  • •

    Endocytoscopy allows visualization of the superficial mucosal layer. Endoscope-integrated and probe-based devices are available, allowing magnification of the mucosa up to 1400-fold.


  • •

    Endomicroscopy can differentiate histologic changes of Crohn’s disease (CD) and ulcerative colitis (UC) in vivo in real time and allows for a targeted and tactical biopsy approach.


  • •

    Endocytoscopy can discriminate mucosal inflammatory cells during endoscopy and allows determination of histopathologic activity of UC.


  • •

    Molecular imaging with fluorescence-labeled probes against disease-specific receptors will enable individualized management of patients with inflammatory bowel disease (IBD).






Introduction


The incidence of inflammatory bowel diseases (IBDs) with its main entities, CD and UC, is rising. Population-based studies suggest that the overall IBD incidence is 29.6 per 100,000, affecting approximately 1.4 million Americans. Patients with IBD suffer from abdominal pain, diarrhea, and often a depressive mood. Moreover, evidence suggests that patients with both UC and CD are at an increased risk for the development of colorectal cancer (CRC). The overall prevalence of CRC in UC patients was recently analyzed in a large meta-analysis and estimated to be 3.7%. CRC is the cause of death in approximately 15% of IBD patients. In this context, it has been shown that patients with course of disease longer than 10 years, pancolitis, left-sided UC, or more proximal disease are at an increased risk. In addition, high rates of multifocal dysplasia and metachronous neoplasia aggravate endoscopic surveillance strategies in these patients. In an attempt to increase diagnostic outcomes of IBD patients, various endoscopic approaches have been introduced. These include red flag technologies, such as magnification endoscopy; dye-based chromoendoscopy techniques (ie, methylene blue and toluidine blue); and dye-less chromoendoscopy techniques, like narrow band imaging (NBI, Olympus, Tokyo, Japan), Fuji Intelligent Color Enhancement (FICE) (Fujifilm, Tokyo, Japan), and i-scan (Pentax Medical, Tokyo, Japan). In addition, several high-resolution endoscopic imaging techniques have been developed, enabling endoscopists to obtain a virtual histology during ongoing endoscopy. These so-called optical biopsy techniques include confocal laser endomicroscopy (CLE; Figs. 1–3 ) and endocytoscopy ( Fig. 4 ).




Fig. 1


( A ) CLE of noninflamed mucosa using the iCLE. Colonic crypts, surrounded by dark-appearing goblet cells, became evident. ( B ) Noninflamed mucosa in IBD visualized with the handheld endomicroscopy system (pCLE). Confocal imaging displays colonic crypts and microvessels within the lamina propria.



Fig. 2


Confocal imaging using iCLE of inflamed mucosa in IBD. Colonic crypts are variously shaped and irregular. Fluorescein sodium leaked into the lamina propria, thereby highlighting the damage of minute mucosal microvessels.



Fig. 3


Using pCLE, mucosal gaps appearing as white incisions of the mucosal surface can be visualized. These gaps are predictive of an acute flare of the disease within the next 12 months.



Fig. 4


Endocytoscopy allows assessment of cytologic features, such as the density of cells, the size and shape of nuclei, and the nucleus-to-cytoplasm ratio ( A ). The colonic architecture is clearly visible ( B ).


This review focuses on CLE and endocytoscopy for the management of patients with IBD.




Introduction


The incidence of inflammatory bowel diseases (IBDs) with its main entities, CD and UC, is rising. Population-based studies suggest that the overall IBD incidence is 29.6 per 100,000, affecting approximately 1.4 million Americans. Patients with IBD suffer from abdominal pain, diarrhea, and often a depressive mood. Moreover, evidence suggests that patients with both UC and CD are at an increased risk for the development of colorectal cancer (CRC). The overall prevalence of CRC in UC patients was recently analyzed in a large meta-analysis and estimated to be 3.7%. CRC is the cause of death in approximately 15% of IBD patients. In this context, it has been shown that patients with course of disease longer than 10 years, pancolitis, left-sided UC, or more proximal disease are at an increased risk. In addition, high rates of multifocal dysplasia and metachronous neoplasia aggravate endoscopic surveillance strategies in these patients. In an attempt to increase diagnostic outcomes of IBD patients, various endoscopic approaches have been introduced. These include red flag technologies, such as magnification endoscopy; dye-based chromoendoscopy techniques (ie, methylene blue and toluidine blue); and dye-less chromoendoscopy techniques, like narrow band imaging (NBI, Olympus, Tokyo, Japan), Fuji Intelligent Color Enhancement (FICE) (Fujifilm, Tokyo, Japan), and i-scan (Pentax Medical, Tokyo, Japan). In addition, several high-resolution endoscopic imaging techniques have been developed, enabling endoscopists to obtain a virtual histology during ongoing endoscopy. These so-called optical biopsy techniques include confocal laser endomicroscopy (CLE; Figs. 1–3 ) and endocytoscopy ( Fig. 4 ).




Fig. 1


( A ) CLE of noninflamed mucosa using the iCLE. Colonic crypts, surrounded by dark-appearing goblet cells, became evident. ( B ) Noninflamed mucosa in IBD visualized with the handheld endomicroscopy system (pCLE). Confocal imaging displays colonic crypts and microvessels within the lamina propria.



Fig. 2


Confocal imaging using iCLE of inflamed mucosa in IBD. Colonic crypts are variously shaped and irregular. Fluorescein sodium leaked into the lamina propria, thereby highlighting the damage of minute mucosal microvessels.



Fig. 3


Using pCLE, mucosal gaps appearing as white incisions of the mucosal surface can be visualized. These gaps are predictive of an acute flare of the disease within the next 12 months.



Fig. 4


Endocytoscopy allows assessment of cytologic features, such as the density of cells, the size and shape of nuclei, and the nucleus-to-cytoplasm ratio ( A ). The colonic architecture is clearly visible ( B ).


This review focuses on CLE and endocytoscopy for the management of patients with IBD.




Technical aspects of CLE


CLE is based on tissue illumination with a low-power laser after application of fluorescence agents, which can either be applied topically (ie, cresyl violet or acriflavine hydrochloride) or systemically (fluorescein sodium). Fluorescein sodium in a dilution of 10% is the most commonly used fluorescence agent. After intravenous injection, fluorescein highlights the extracellular matrix. Adverse events are rare. One recent multicenter study reported transient hypotension without shock (0.5% of patients), nausea (0.39%), injection site erythema (0.35%), self-limited diffuse rash (0.04%), and mild epigastric pain (0.09%). To visualize the cell nucleus fluorescein sodium can be combined with topical application of acriflavine hydrochloride. This dye agent allows for a detailed analysis of the nucleus-to-cytoplasm ratio for diagnosis and grading of intraepithelial neoplasia. Because acriflavine accumulates in nuclei, concerns have been raised regarding a potential mutagenic risk of the drug. Alternatively, cresyl violet can be applied. By cytoplasmic enrichment of cresyl violet, nuclear morphology could be negatively visualized.


Two CE-approved and Food and Drug Administration–approved endomicroscopy devices are available for the daily use in clinical practice. One is integrated into the distal tip of a standard high-resolution video gastroscope or colonoscope (iCLE, Pentax Medical, Tokyo, Japan) and one is probe-based, capable of passage through the working channel of a standard endoscope (pCLE, Cellvizio, Mauna Kea Technologies, Paris, France).


Both systems use an incident 488-nm wavelength laser system. iCLE collects images at a manually adjustable scan rate of 1.6 frames per second with a maximum resolution of 1024 × 1024 pixels (1 megapixel). By pushing a button on the handle of the endoscope, the scanning depth (ranging from 0 μm to 250 μm) and the laser power (ranging from 0 μW to 1000 μW) can be dynamically adjusted. For pCLE, different probes for various indications are available. pCLE devices use a fixed laser power and a fixed imaging plane depth. Confocal images are streamed at a frame rate of 12 frames per second, thereby obtaining real-time videos of the intestinal mucosa. A special computer algorithm (mosaicing) allows reconstruction of single video frames either in real time or postprocessed with an increased field of view of up to 4 mm × 2 mm. Table 1 provides an overview of main technical aspects of both CLE devices.



Table 1

Technical aspects of iCLE and pCLE
































iCLE pCLE
Outer diameter (mm) 12.8 1.0; 2.7; 2.6 a
Length (cm) 120; 180 400; 300 a
Field of view (μm) 475 × 475 320; 240; 600 μm 2 a
Resolution 0.7 3.5; 1.0 a
Magnification ×1000 ×1000
Imaging plane depth (μm) 0–250 (dynamic) 40–70; 55–65; 70–130 (fixed) a

a Dependent on various probes. For detailed information, see Neumann and colleageus.



One recent study prospectively assessed the learning curve of CLE in patients with IBD. Overall, 26 consecutive patients were included. A significant improvement of CLE performance parameters was observed over time, including decreased confocal imaging time, successful CLE diagnosis, and decline in procedural time. Performance parameters improved significantly after the initial 3 cases. Therefore, it was concluded that CLE may represent an easy-to-learn novel diagnostic method for in vivo analysis of mucosal changes in IBD.




Two different endomicroscopy systems exist. One is integrated into a standard, high-resolution endoscope (iCLE) and one is probe-based, capable of passage through the working channel of a standard endoscope (pCLE).

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Sep 12, 2017 | Posted by in GASTOINESTINAL SURGERY | Comments Off on Endomicroscopy and Endocytoscopy in IBD

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